A5051590111- Trace Elements in Health
- Iron Metabolism and Disorders
- Fungal and yeast genetics research
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- Photosynthetic Processes and Mechanisms
- Heme Oxygenase-1 and Carbon Monoxide
- Plant Micronutrient Interactions and Effects
- Porphyrin Metabolism and Disorders
- Biofuel production and bioconversion
- Hemoglobinopathies and Related Disorders
- Microbial Metabolic Engineering and Bioproduction
- Neonatal Health and Biochemistry
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Biotin and Related Studies
- Hemoglobin structure and function
- Metabolism and Genetic Disorders
- Cellular transport and secretion
- Aldose Reductase and Taurine
- Folate and B Vitamins Research
- Metabolomics and Mass Spectrometry Studies
- Electrochemical sensors and biosensors
- Genetic Neurodegenerative Diseases
- Research on Leishmaniasis Studies
National Institute of Diabetes and Digestive and Kidney Diseases
2007-2023
National Institutes of Health
2009-2023
Institute of Cell Biology
2002-2007
National Academy of Sciences of Ukraine
1999-2000
Palladin Institute of Biochemistry
1999-2000
Background and Aims Iron is essential yet also highly chemically reactive potentially toxic. The mechanisms that allow cells to use iron safely are not clear; defects in management a causative factor the cell‐death pathway known as ferroptosis. Poly rC binding protein 1 (PCBP1) multifunctional serves cytosolic chaperone, transferring recipient proteins mammalian cells. Although PCBP1 distributes cells, its role managing tissues remains open for study. liver specialized uptake, utilization,...
Iron is an essential cofactor for enzymes involved in numerous cellular processes, yet little known about the impact of iron deficiency on metabolism or proteins. Previous studies have focused changes transcript and proteins levels iron-deficient cells, these may not reflect transport activity flux through a metabolic pathway. We analyzed metabolomes transcriptomes yeast grown iron-rich iron-poor media to determine which biosynthetic processes are altered when availability falls. led glucose...
Developing erythrocytes take up exceptionally large amounts of iron, which must be transferred to mitochondria for incorporation into heme. This massive iron flux precisely controlled permit the coordinated synthesis heme and hemoglobin while avoiding toxic effects chemically reactive iron. In cultured animal cells, chaperones poly rC–binding protein 1 (PCBP1) PCBP2 deliver ferritin, sole cytosolic storage protein, nuclear receptor coactivator 4 (NCOA4) mediates autophagic turnover ferritin....
Analysis of iron-regulated gene expression in<i>Saccharomyces cerevisiae</i> using cDNA microarrays has identified three putative cell wall proteins that are directly regulated by Aft1p, the major iron-dependent transcription factor in yeast. <i>FIT1</i>, <i>FIT2</i>, and<i>FIT3</i> (for facilitator irontransport) were more highly expressed strains grown low concentrations iron and which<i>AFT1–1<sup>up</sup></i>, a constitutively active allele of<i>AFT1</i>, was expressed. Northern blot...
Trypanosomatid protozoan parasites lack a functional heme biosynthetic pathway, so must acquire from the environment to survive. However, molecular pathway responsible for acquisition by these organisms is unknown. Here we show that L. amazonensis LHR1, homolog of C. elegans plasma membrane transporter HRG-4, functions in transport. Tagged LHR1 localized and endocytic compartments, both mammalian cells. Heme deprivation increased transcript levels, promoted uptake fluorescent analog ZnMP,...
Significance Poly(rC)-binding protein 1 (PCBP1) regulates multiple cellular processes; many studies have focused on its role in tumor formation and metastasis through capacity to bind nucleic acids. PCBP1 binds DNA RNA mediates interactions with other proteins that affect transcription messenger processing. is also an iron chaperone. It cytosolic as Fe–glutathione complex controls the chemical reactivity, sensing, trafficking of cell. How are these distinct activities coordinated a single...
Voltage-dependent anion channel (VDAC) is the major pathway for transport of ions and metabolites across mitochondrial outer membrane. Among three known mammalian VDAC isoforms, VDAC3 least characterized, but unique functional roles have been proposed in cellular animal models. Yet, a high-sequence similarity between VDAC1 indicative similar pore-forming structure. Here, we conclusively show that forms stable, highly conductive voltage-gated channels that, much like VDAC1, are weakly...
Saccharomyces cerevisiae responds to iron deprivation by increasing the transcription of genes involved in uptake environmental and mobilization vacuolar stores. HMX1 is also transcribed under conditions control major iron-dependent factor, Aft1p. Although Hmx1p exhibits limited homology heme oxygenases, it has not been shown be enzymatically active. We find that a resident protein endoplasmic reticulum isolated yeast membranes contain degradation activity dependent on HMX1. facilitates...
Although Candida albicans and Saccharomyces cerevisiae express very similar systems of iron uptake, these species differ in their capacity to use heme as a nutritional source. Whereas C. efficiently takes up heme, S. grows poorly on media containing the sole source iron. We identified gene from that would enhance uptake when expressed cerevisiae. Overexpression CaFLC1 (for flavin carrier 1) stimulated growth In albicans, deletion both alleles resulted decrease activity, whereas...
Unlike pathogenic fungi, the budding yeast Saccharomyces cerevisiae is not efficient at using heme as a nutritional source of iron. Here we report that for this yeast, uptake induced under conditions starvation. Heme synthesis requires oxygen, and grown anaerobically exhibited an increased hemin. Similarly, strain lacking aminolevulinate synthase sixfold increase in hemin when without 2-aminolevulinic acid. We used microarray analysis cells reduced oxygen tension or intracellular to identify...
Caenorhabditis elegans and human HRG-1-related proteins are conserved, membrane-bound permeases that bind translocate heme in metazoan cells via a currently uncharacterized mechanism. Here, we show cellular import of by from worms humans requires strategically located amino acids topologically conserved across species. We exploit synthesis-defective Saccharomyces cerevisiae mutant to model the auxotrophy C. demonstrate that, under heme-deplete conditions, endosomal CeHRG-1 both specific...
Abstract Iron deficiency causes oversynthesis of riboflavin in several yeast species, known as flavinogenic yeasts. However, the mechanisms such regulation are not known. We found that mutations causing overproduction and iron hyperaccumulation ( rib80, rib81 hit1 ), well cobalt excess or all provoke oxidative stress Pichia guilliermondii yeast. content cells, production both malondialdehyde by P. wild type mutant strains depend on a carbon source used cultivation media. The data suggest...
Pichia guilliermondii is a representative of group so-called flavinogenic yeast species that overproduce riboflavin (vitamin B(2)) in response to iron limitation. Using insertion mutagenesis, we isolated P. mutants overproducing riboflavin. Analysis nucleotide sequence recombination sites revealed cassettes integrated into the genome disrupting genes similar VMA1 gene Ashbya gossypii and Saccharomyces cerevisiae FES1 FRA1 S. cerevisiae. The constructed guilliermondiiΔvma1-17 mutant possessed...